Cargando…

HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription

Studies have shown that cancer stem cells (CSCs) are involved in resistance and metastasis of cancer; thus, therapies targeting CSCs have been proposed. Here, we report that heat shock 70-kDa protein 1-like (HSPA1L) is partly involved in enhancing epithelial–mesenchymal transition (EMT) and CSC-like...

Descripción completa

Detalles Bibliográficos
Autores principales: Choi, Soo-Im, Lee, Jei-Ha, Kim, Rae-Kwon, Jung, Uhee, Kahm, Yeon-Jee, Cho, Eun-Wie, Kim, In-Gyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555772/
https://www.ncbi.nlm.nih.gov/pubmed/32971893
http://dx.doi.org/10.3390/ijms21186957
_version_ 1783594085385240576
author Choi, Soo-Im
Lee, Jei-Ha
Kim, Rae-Kwon
Jung, Uhee
Kahm, Yeon-Jee
Cho, Eun-Wie
Kim, In-Gyu
author_facet Choi, Soo-Im
Lee, Jei-Ha
Kim, Rae-Kwon
Jung, Uhee
Kahm, Yeon-Jee
Cho, Eun-Wie
Kim, In-Gyu
author_sort Choi, Soo-Im
collection PubMed
description Studies have shown that cancer stem cells (CSCs) are involved in resistance and metastasis of cancer; thus, therapies targeting CSCs have been proposed. Here, we report that heat shock 70-kDa protein 1-like (HSPA1L) is partly involved in enhancing epithelial–mesenchymal transition (EMT) and CSC-like properties in non-small cell lung cancer (NSCLC) cells. Aldehyde dehydrogenase 1 (ALDH1) is considered a CSC marker in some lung cancers. Here, we analyzed transcriptional changes in genes between ALDH1high and ALDH1low cells sorted from A549 NSCLC cells and found that HSPA1L was highly expressed in ALDH1high cells. HSPA1L played two important roles in enhancing CSC-like properties. First, HSPA1L interacts directly with IGF1Rβ and integrin αV to form a triple complex that is involved in IGF1Rβ activation. HSPA1L/integrin αV complex-associated IGF1Rβ activation intensified the EMT-associated cancer stemness and γ-radiation resistance through its downstream AKT/NF-κB or AKT/GSK3β/β-catenin activation pathway. Secondly, HSPA1L was also present in the nucleus and could bind directly to the promoter region of β-catenin to function as a transcription activator of β-catenin, an important signaling protein characterizing CSCs by regulating ALDH1 expression. HSPA1L may be a novel potential target for cancer treatment because it both enhances IGF1Rβ activation and regulates γβ-catenin transcription, accumulating CSC-like properties.
format Online
Article
Text
id pubmed-7555772
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75557722020-10-19 HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription Choi, Soo-Im Lee, Jei-Ha Kim, Rae-Kwon Jung, Uhee Kahm, Yeon-Jee Cho, Eun-Wie Kim, In-Gyu Int J Mol Sci Article Studies have shown that cancer stem cells (CSCs) are involved in resistance and metastasis of cancer; thus, therapies targeting CSCs have been proposed. Here, we report that heat shock 70-kDa protein 1-like (HSPA1L) is partly involved in enhancing epithelial–mesenchymal transition (EMT) and CSC-like properties in non-small cell lung cancer (NSCLC) cells. Aldehyde dehydrogenase 1 (ALDH1) is considered a CSC marker in some lung cancers. Here, we analyzed transcriptional changes in genes between ALDH1high and ALDH1low cells sorted from A549 NSCLC cells and found that HSPA1L was highly expressed in ALDH1high cells. HSPA1L played two important roles in enhancing CSC-like properties. First, HSPA1L interacts directly with IGF1Rβ and integrin αV to form a triple complex that is involved in IGF1Rβ activation. HSPA1L/integrin αV complex-associated IGF1Rβ activation intensified the EMT-associated cancer stemness and γ-radiation resistance through its downstream AKT/NF-κB or AKT/GSK3β/β-catenin activation pathway. Secondly, HSPA1L was also present in the nucleus and could bind directly to the promoter region of β-catenin to function as a transcription activator of β-catenin, an important signaling protein characterizing CSCs by regulating ALDH1 expression. HSPA1L may be a novel potential target for cancer treatment because it both enhances IGF1Rβ activation and regulates γβ-catenin transcription, accumulating CSC-like properties. MDPI 2020-09-22 /pmc/articles/PMC7555772/ /pubmed/32971893 http://dx.doi.org/10.3390/ijms21186957 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, Soo-Im
Lee, Jei-Ha
Kim, Rae-Kwon
Jung, Uhee
Kahm, Yeon-Jee
Cho, Eun-Wie
Kim, In-Gyu
HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription
title HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription
title_full HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription
title_fullStr HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription
title_full_unstemmed HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription
title_short HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription
title_sort hspa1l enhances cancer stem cell-like properties by activating igf1rβ and regulating β-catenin transcription
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555772/
https://www.ncbi.nlm.nih.gov/pubmed/32971893
http://dx.doi.org/10.3390/ijms21186957
work_keys_str_mv AT choisooim hspa1lenhancescancerstemcelllikepropertiesbyactivatingigf1rbandregulatingbcatenintranscription
AT leejeiha hspa1lenhancescancerstemcelllikepropertiesbyactivatingigf1rbandregulatingbcatenintranscription
AT kimraekwon hspa1lenhancescancerstemcelllikepropertiesbyactivatingigf1rbandregulatingbcatenintranscription
AT junguhee hspa1lenhancescancerstemcelllikepropertiesbyactivatingigf1rbandregulatingbcatenintranscription
AT kahmyeonjee hspa1lenhancescancerstemcelllikepropertiesbyactivatingigf1rbandregulatingbcatenintranscription
AT choeunwie hspa1lenhancescancerstemcelllikepropertiesbyactivatingigf1rbandregulatingbcatenintranscription
AT kimingyu hspa1lenhancescancerstemcelllikepropertiesbyactivatingigf1rbandregulatingbcatenintranscription